Mesenchymal stem/stromal cells (MSCs) are multipotent cells located in different areas of the human body. The oral cavity is considered a potential source of MSCs because they have been identified in several dental tissues (D-MSCs). Clinical trials in which cells from these sources were used have shown that they are effective and safe as treatments for tissue regeneration. Importantly, immunoregulatory capacity has been observed in all of these populations; however, this function may vary among the different types of MSCs. Since this property is of clinical interest for cell therapy protocols, it is relevant to analyze the differences in immunoregulatory capacity, as well as the mechanisms used by each type of MSC. Interestingly, D-MSCs are the most suitable source for regenerating mineralized tissues in the oral region. Furthermore, the clinical potential of D-MSCs is supported due to their adequate capacity for proliferation, migration, and differentiation. There is also evidence for their potential application in protocols against autoimmune diseases and other inflammatory conditions due to their immunosuppressive capacity. Therefore, in this review, the immunoregulatory mechanisms identified at the preclinical level in combination with the different types of MSCs found in dental tissues are described, in addition to a description of the clinical trials in which MSCs from these sources have been applied.

Introduction: Human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are often combined with calcium phosphate (CaP)-based 3D-printed scaffolds with the goal of creating a bone substitute that can repair segmental bone defects. In vitro, the induction of osteogenic differentiation traditionally requires, among other supplements, the addition of β-glycerophosphate (BGP), which acts as a phosphate source. The aim of this study is to investigate whether phosphate contained within the 3D-printed scaffolds can effectively be used as a phosphate source during hBM-MSC in vitro osteogenesis. Methods: hBM-MSCs are cultured on 3D-printed discs composed of poly (lactic-co-glycolic acid) (PLGA) and β-tricalcium phosphate (β-TCP) for 28 days under osteogenic conditions, with and without the supplementation of BGP. The effects of BGP removal on various cellular parameters, including cell metabolic activity, alkaline phosphatase (ALP) presence and activity, proliferation, osteogenic gene expression, levels of free phosphate in the media and mineralisation, are assessed. Results: The removal of exogenous BGP increases cell metabolic activity, ALP activity, proliferation, and gene expression of matrix-related (COL1A1, IBSP, SPP1), transcriptional (SP7, RUNX2/SOX9, PPARγ) and phosphate-related (ALPL, ENPP1, ANKH, PHOSPHO1) markers in a donor dependent manner. BGP removal leads to decreased free phosphate concentration in the media and maintained of mineral deposition staining. Discussion: Our findings demonstrate the detrimental impact of exogenous BGP on hBM-MSCs cultured on a phosphate-based material and propose β-TCP embedded within 3D-printed scaffold as a sufficient phosphate source for hBM-MSCs during osteogenesis. The presented study provides novel insights into the interaction of hBM-MSCs with 3D-printed CaP based materials, an essential aspect for the advancement of bone tissue engineering strategies aimed at repairing segmental defects.

For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.

Oromaxillofacial tissues (OMT) are composed of tooth and bone, together with nerves and blood vessels. Such a composite material is a huge source for mesenchymal stem cells (MSCs) that can be obtained with ease from extracted teeth, teeth structures and socket blood, flapped gingiva tissue, and mandibular/maxillar bone marrow. They offer a biological answer for restoring damaged dental tissues such as the regeneration of alveolar bone, prevention of pulp tissue defects, and dental structures. Dental tissue-derived mesenchymal stem cells share properties with bone marrow-derived mesenchymal stem cells and there is a considerable potential for these cells to be used in different stem cell-based therapies, such as bone and nerve regeneration. Dental pulp tissue might be a very good source for neurological disorders whereas gingiva-derived mesenchymal stem cells could be a good immune modulatory/suppressive mediators. OMT-MSCs is also promising candidates for regeneration of orofacial tissues from the perspective of developmental fate. Here, we review the fundamental biology and potential for future regeneration strategies of MSCs in oromaxillofacial research.

Resection of maxillofacial may cause a series of complications such as loss of facial deformity, dysfunction, and psychological distress. Mandibular reconstruction following resection still remains difficult.

A 18-year-old male patient with mandibular ameloblastoma was admitted in the hospital of stomatology. The tumor was dissected and the defect was reconstructed using vascularized fibula graft. One year later, distraction osteogenesis (DO) was performed on the fibula graft to augment the alveolar bone for dental implants. Panoramic radiographs, computed tomography, and clinical photographs were taken. Five months after completion of distraction, the distraction device was removed.

Panoramic radiographs, computed tomography, and clinical photographs showed the good healing after fibula graft for mandibular reconstruction following ameloblastoma ablation and satisfied alveolar bone with good width and height for dental implants after DO.

This report suggests that DO of fibula graft following mandibular reconstruction was an efficient method to augment the alveolar bone for dental implants.

Disease of, or trauma to, the human jaw account for thousands of reconstructive surgeries performed every year. One of the most popular and successful treatment options in this context involves the transplantation of bone tissue from a different anatomical region into the affected jaw. Although, this method has been largely successful, the integration of the new bone into the existing bone is often imperfect, and the integration of the host soft tissues with the transplanted bone can be inconsistent, resulting in impaired function. Unlike humans, several vertebrate species, including fish and amphibians, demonstrate remarkable regenerative capabilities in response to jaw injury. Therefore, with the objective of identifying biological targets to promote and engineer improved outcomes in the context of jaw reconstructive surgery, we explore, compare and contrast the natural mechanisms of endogenous jaw and limb repair and regeneration in regenerative model organisms. We focus on the role of different cell types as they contribute to the regenerating structure; how mature cells acquire plasticity in vivo; the role of positional information in pattern formation and tissue integration, and limitations to endogenous regenerative and repair mechanisms.